Background: A Low level of Response (LR) to alcohol is genetically influenced and is a possible predictor of alcohol use disorder (AUD). Further, alcohol’s stimulating and rewarding responses have been found to predict increased binge drinking frequency and AUD risk among social drinkers. However, this relationship has not been examined in Asian samples. Moreover, variations in the alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase (ALDH2) genes may influence the LR to alcohol by increasing levels of acetaldehyde during alcohol metabolism. This presentation will examine: 1) the relationship between the genetic variation of ADH1B and ALDH2 and subjective response to alcohol and 2) the association between the subjective response to alcohol, personality traits and AUD risk in Japanese young adults studied prospectively.

Methods: Subjects included 424 healthy Japanese college students aged 20-23 years old. Using the alcohol clamp method, we infused diluted alcohol (6%) to maintain a blood alcohol concentration (BAC) at 50 ± 5 mg% for 3 hours. The LR to alcohol was assessed using the Biphasic Alcohol Effects Scale (BAES). Personality traits were assessed by Temperament and Character Inventory (TCI) and Maudsley Personality Inventory (MPI). Subjects have been followed every year using the Alcohol Use Disorder Identification Test (AUDIT).

Results: Subjects with inactive ALDH2 showed stronger sedative subjective responses to alcohol than those with active ALDH2; however, we did not find any differences in the stimulant effects of alcohol between subjects with active and inactive ALDH2. Examining the relationship between subjective response to alcohol and AUDIT scores at follow up revealed that subjects with higher (≥ 8) AUDIT scores showed stronger stimulant, but weaker sedative, subjective responses to alcohol than those with lower AUDIT scores. Higher novelty seeking and lower harm avoidance on TCI and higher extraversion and lower neuroticism on MPI were associated with higher AUDIT scores, but these relationships differed by gender.

Conclusion: Our findings suggest that a subjective stimulant response to alcohol predicts later alcohol related problems among healthy young Japanese adults and also suggest that personality might influence subjective response to alcohol as well as alcohol-related problems at follow-up.